The cardiovascular and respiratory responses to dynamic exercise are thought to be controlled in part by information from central neural locations (central command) and in part by information from contracting skeletal muscle (peripheral feedback). The research proposed in this application will attempt to describe the role of a selected central neural location which is thought to be involved in the central command of cardiovascular function during exercise. More specifically, the proposed studies will examine the role of the fields of Forel in mediating cardiovascular responses evoked by dynamic exercise. An initial series of experiments will be performed on anesthetized dogs. In these experiments, the fields of Forel will be stimulated electrically and chemically, procedures which are thought to produce cardiovascular effects similar to those produced by central command in the conscious animal. Cardiovascular variables, including regional blood flow distribution, will be measured during electrical stimulation in this subthalamic site. Animals will be studied in the unblocked state and during alpha- and/or beta-adrenergic blockade. As additional controls, sites in the lateral hypothalamus will be stimulated electrically and selected drugs will be injected in the fields of Forel. In a second series of experiments, adult beagels will be instrumented to permit repeated measurement of cardiovascular variables during dynamic exercise on a motor-driven treadmill. The beagles will then be studied during submaximal and maximal exercise before and after making lesions in the fields of Forel. Variables which will be measured or calculated include heart rate, cardiac output, arterio-venous oxygen difference, oxygen consumption, left ventricular pressure, and left ventricular dP/dt. Adult beagles will also be used in the final series of experiments proposed in this application. In these latter studies, regional blood flow at rest and during maximal exercise will be measured with the radioactive microsphere technique before and after making lesions in the fields of Forel. The results of the three series of experiments should provide valuable knowledge regarding the role of the fields of Forel in the overall control of cardiovascular function during exercise. Additionally, the knowledge obtained from these studies may have clinical relevance for patients who are impaired neurologically and display abnormal responses to the stress of dynamic exercise.
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